Abstract

On one side, pregnancy is a bliss, a beautiful journey for most women while on
other, it increases the risk of several diseases which may cause considerable
morbidity and mortality in young women in the most productive period of their
lives. Neurological emergencies in pregnancy often have grave prognosis and so,
must be promptly diagnosed and treated. This article reviews the clinical features
and management of some of the common severe neurological emergencies in
pregnancy.

Introduction

Neurological complicat ions of
pregnancy may turn out emergent.1
However, several diseases have
increased prevalence during pregnancy or postpartum period. These diseases
may either be unique to the pregnant/
postpartum state like preeclampsia and
delivery-associated neuropathies else
may be indirectly related to pregnancy,
such as cerebral venous thrombosis,
ischemic stroke, and intracerebral
hemorrhage. Hence, it is vital for the
treating clinician to have a sound
diagnostic approach towards these
neurological emergencies. Moreover,
being the health issue of young
individuals, social, epidemiological
and medico-legal impact of pregnancy
related adverse outcomes is often high.
This article intends to review those
serious neurological diseases which
are commonly seen during pregnancy
and the postpartum period2 (Table 1).

Migraine

Migraine is commonly prevalent
among women of childbearing age and
often can be severe enough in pregnancy.
Severe migraine may present as ‘status migrainosus’(headache beyond 72 hrs
at a stretch). Infrequently, migraine
may occur for the first time during
pregnancy . However , migraine
incidence usually more common in
first trimester appears to be reduced
during the second and third trimesters,
new onset aura may appear during
that time trimester of pregnancy.3,4,6
Migraine doesn’t significantly affect
fertility or pregnancy outcomes, but it
is associated with a risk of preeclampsia
or stroke.3,5

Medical therapy usually include
analgesics such as acetaminophen,
steroids, and if necessary, opiate
medications.5 Antiemetic therapy
may include metoclopramide ,
ondansetron and sedating agents such
as promethazine and chlorpromazine.5,7
Triptans, are probably safe in pregnancy
but may slightly affect preterm labor
rates.8 However, given the limited
safety data available, triptan therapy
cannot be recommended.5,8

Stroke in pregnancy

Pregnancy contributes to the risk of
a cerebrovascular event.9,10 Pregnancy
is a hypercoagulable state because
of increased platelet aggregability, fibrinogen levels and factors VIII,
IX and X. Fibrinolytic activity is
decreased with a reduction in the levels
of endogenous anticoagulants, like
protein S and antithrombin III. These
changes persist into the early postpartum
period. Consequently, majority
of the ischemic strokes occur late in
pregnancy and particularly in the
postpartum period.11,12 Hypertension,
which is associated with ischemic
as well as hemorrhagic strokes, is
a primary feature of preeclampsia.
Pregnancy, in itself, is a state of
induced hypercoagulability which
may facilitate the development of
venous thromboemboli in a susceptible
individual.13 Paradoxical embolism
related to the presence of a patent
foramen ovale (PFO) sometimes gets
triggered by both the coagulation profile
changes and by the hemodynamic
changes such as increased venous
stasis.13 Peripartum cardiomyopathy
is a rare complication of pregnancy
but may cause cardioembolic stroke
and severe progressive cardiac failure
requiring transplant.13 Etiologies of
stroke unique to pregnancy include
choriocarcinoma , postpartum
cerebral angiopathy and postpartum
cardiomyopathy. Stroke during labor
or soon after vaginal delivery may
result from an amniotic fluid embolus.
Abortions and obstetric procedures
performed outside medical standards
may cause vaginal air insufflations,
thus resulting air embolus to the heart,
with subsequent generalized and focal
cerebral ischemia.14

Stroke patients usually present
with abrupt onset of focal neurological
deficits (hemiparesis, hemianaesthesia,
ataxia, blindness). However, at times,
patients may present with non-focal
symptoms like headache, seizures and
altered consciousness. These symptoms
are more frequently observed in
patients with venous thrombosis and
resulting venous infarctions.15,16

The primary treatment for acute
ischemic stroke is intravenous
thrombolysis with tissue plasminogen
activator (tPA). However, pregnant
patients were not included in tPA
clinical trials. There have been concerns
regarding the adverse effects of tPA
on the pregnant mother and fetus
like placental abruption, abortion,
uterine hemorrhage and preterm
delivery as well as hemorrhage
including intracerebral hemorrhage.However, with scientific data available,
it appears that maternal mortality,
preterm delivery and fetal loss are
infrequent.17-19

Hemorrhagic stroke is of
lower incidence in pregnancy as
compared to ischemic stroke and
occurs mostly during late pregnancy
and the puerperium. Intracerebral
hemorrhage has a higher maternal
mortality rate, nearly accounting
for 5% to 12% of overall maternal
mortality in pregnancy.11 Hemorrhage
is often associated with preeclampsia /
eclampsia, arteriovenous malformations
(AVM,) and aneurysmal rupture.20 In
case of an unruptured AVM, risk of first
hemorrhagic event during pregnancy
is about 3.5%, no higher than over a
similar period outside pregnancy.21
Aneurysmal rupture is more likely in
the second and third trimesters (30%
and 55% of ruptures respectively),
as compared with first trimester or
puerperium (6% and 9% respectively).22
The possible etiology for the heightened
risk of intracerebral hemorrhage (ICH)
during pregnancy may relate to the
physiological changes of pregnancy
including increased blood volume,
rising blood pressure, and changes in
vascular tone. The physical stress of
delivery and labor may also contribute
to the risk of aneurysmal rupture,
and patients with known aneurysms
and AVMs are often delivered by
scheduled C-section. Treatment include
antihypertensives and antiseizure
medications including magnesium,
with close monitoring.13,24,23

Eclampsia

Worldwide, the incidence of
preeclampsia ranges between 2% and
10% of pregnancies. The incidence
of preeclampsia, the precursor to
eclampsia, varies greatly worldwide.
WHO estimates the incidence
of preeclampsia to be seven times
higher in developing countries (2.8%
of live births) than in developed
countries (0.4%).25 Preeclampsia is
defined by proteinuria and gestational
hypertension which usually occurs after
the 20th week of pregnancy. Severe
cases may manifest with headache,
visual changes, other signs of raised
intracranial pressure and reduced fetal
growth.26,27 The underlying etiology for
preeclampsia and eclampsia remain
unknown, but abnormal immunological
interactions between foetal and
maternal tissues appear to be involved.28

Eclampsia is conventionally
characterized by the new onset seizures
and/or coma during the pregnancy,
labor, or puerperium in the background
of preeclampsia.

Recently researchers found favor
with the opinion that seizures usually
occur without the pre-existing setting
of preeclampsia, particularly in late
postpartum eclampsia. 30

In severe pre-eclampsia and
eclampsia, prompt delivery is the
immediate goal.29 Thus, treatment
strategies include control of arterial
blood pressure, reduction of cerebral
oedema, and rapid control and
prevention of seizures. Magnesium
sulphate is being commonly used
in pre-eclampsia and eclampsia.
Ongoing seizures should be aborted
with intravenous diazepam 5-10 mg
or lorazepam 2-4 mg given as slow
intravenous bolus, while phenytoin
may prevent recurrent seizures.
Chlormethiazole is not commonly used
nowadays.

Myasthenia Gravis

Myasthenia gravis (MG) is a
chronic disease which affects the
neuromuscular transmission resulting
in fatigable weakness of the skeletal
muscles. Women are more commonly
affected with the disorder (2:1).31 The
course of MG during pregnancy is
variable and varies with subsequent
pregnancies.32 Exacerbations occur in
nearly 40% of pregnancies with the
remainder of patients having stable
disease or remission of symptoms.33
The neuromuscular blockade occurs
due to an autoimmune mechanism,
and anti-acetylcholine receptor (AChR)
antibody is detectable in 90% of affected
patients.34 Antistriated muscle antibody
is often associated with an underlying
thymoma.

In the pre-thymectomy era, one third
of myasthenic patients deteriorated
during their pregnancies, one third had
their health unchanged, and one third
improved.35 Thymectomy is indicated
for thymoma and is recommended in
all young myasthenic patients who
have a deteriorating response to an
anticholinesterase drug.35 The thymoma
should be resected prior to a planned
pregnancy;

Steroid-sparing immunosuppressant
drugs such as azathioprine should
be discontinued prior to pregnancy
owing to the risk of teratogenicity.35
Corticosteroid therapy also poses a
risk to the mother and the foetus. The
oral or intramuscular administration
of pyridostigmine and neostigmine is
safe as there is little passage through
the placenta. Azathioprine can induce
fetal leukopenia but is often maintained
for severe disease.

The management of preeclampsia
in myasthenic patients presents a
challenge as magnesium sulfate is
contraindicated. Phenytoin can be a
suitable alternative to manage seizures.31
Vaginal delivery is not contraindicated
but a myasthenic patient may not
be able to tolerate full labor due to
fatigue.31 Following the delivery, infant
must be evaluated for neonatal MG
which may occur in nearly 10% to 20%
of deliveries via placental transmission
of acetylcholine antibodies.36 Neonatal
MG responds well to anticholinesterase
medications.33 Pregnancy does not
worsen the long-term prognosis of
MG.31

Guillain-Barre syndrome (GBS)

GBS represents a heterogeneous
group of immune mediated peripheral
neuropathies.GBS must be kept under
consideration in any pregnant woman
complaining of muscle weakness,
tingling of the fingers, and difficulty
in breathing.37,38
Presentation: Rapidly progressive
symmetric areflexic weakness.
Timing: Any trimester and postpartum
period but is more frequent
in third trimester and initial 2 weeks
after delivery.
Course: Worsen in post partum
period due to delayed type of
hypersensi t i v i t y . 39 Nearly 20%
disability and a maternal mortality of
approximately 7% has been documented
while gbs without pregnancy has a
mortality rate of less than 5%.(40)
Treatment : Intravenous
immunoglobulins (IVIG ) or
plasma pheresis , alongwith
ventilatory support whenever needed.
Plasmapheresis and IVIG significantly
improve patients’ outcome with
complete recovery in almost 70-80% of
the cases.39,41
Obstetric Precaution: Delivery
must be actively coordinated with anesthesiologist as autonomic
instability in some patients
may complicate anesthetic care.43
Additionally, there are reports of
succinyl choline administration
precipitating hyperkalemia and use
should be avoided.42,43

Idiopathic Facial Nerve Palsy

Bell’s palsy occur in approximately
17/100,000 women of child bearing
age per year.44 Overall, Bell’s palsy is
more frequent in females (2-4:1) and
incidence may rise up to 6 times more in
pregnancy as compared to non-pregnant
women, although some of the studies
have found no increase in incidence.45-
47 Bell’s palsy presents mostly during
the third trimester and peripartum.46,47
There appears to be an association
with pre-eclampsia.47,48 Almost 15%
of pregnant women with acute lower
motor neuron facial paralysis may have
secondary etiologies.49 Plasma volume
expansion in pregnancy may result in
increased interstitial fluid which may
lead to mechanical compression of the
facial nerve in fallopian canal. Based on
this hypothesis, Bell’s palsy apparently
has maximum incidence in third
trimester because of the peak increase
in interstitial fluid volume during third
trimester.50,51 Besides, some researchers
have proposed another hypothesis that
hypercoagulable state in pregnancy
may predispose to thrombosis of
vasa nervosum of the facial nerve,
thus leading to devascularization and
ischemic nerve injury.52

Neuropathies

Postpartum neuropathies are
relatively uncommon.Intrinsic obstetric
palsies may result from delivery or labor
process, the most commonly occurring
of which is lateral femoral neuropathy.
Other neuropathies known to occur are
femoral, obturator, sciatic, common
peroneal nerve, and lumbosacral plexus
in descending order of frequency.53
The most apparent cause of these
neuropathies is mechanical stretch in
dorsal lithotomy position. However,
nulliparity and prolonged second
stage of labor have been reported as
important risk factors.53

Cerebral Venous Thrombosis

A rare cause of stroke overall,
cerebral venous thrombosis (CVT) is an
important consideration in pregnancy
and postpartum state.54-57 A spike
in incidence in the first trimester
might be attributable to women who become pregnant with an underlying
thrombophilia.39 However, more
than 75% of cases of CVT are post
partum.58 The main risk factors are
caesarean section, traumatic delivery,
dehydration, anaemia, increased serum
homocysteine and low CSF pressure
due to dural puncture from a neuraxial
anaesthetic.59,60 Pregnancy in itself is a
hypercoagulable state, and thus a risk
factor for thrombotic events.11,13 Other
genetic causes of hypercoagubility
including antiphospholipid syndrome,
prothrombin genemutations ,
and factor V Leiden / MHTFR
deficiency are predisposing factors
for the development of CVT.61 Oral
contraceptive pills (OCP) use is often
associated with CVT and must be
enquired for, especially in young
women presenting with acute headache
and visual changes.62
Superior sagittal and transverse
sinuses are most commonly involved
and may manifest with headache,
seizures, papilledema and other
signs of raised intracranial tension.
The cavernous sinus is infrequently
involved and when thrombosed, may
present with proptosis, cranial nerve
deficits and painful ophthalmoplegia
due to raised pressure inside the
sinus and orbit. CT of brain are often
negative, but 30% of cases might show
a clot or signs of infarction.63 Ischaemic
infarcts often undergo haemorrhagic
transformation. MR venography-along
with gradient echo (GRE) sequencesis
usually diagnostic and often, the
imaging study of choice.63
Anticoagulation with warfarin
is generally avoided in pregnancy
complicated with CVT, especially in first
trimester due to risk of teratogenicity.
Howeve r , t h e American Heart
Association (AHA) recommendations
say that warfarin therapy is safe in
second and third trimester while it
should be discontinued in later stage
of pregnancy.64 Low-dose aspirin is felt
to be safe, particularly after the first
trimester, according to the American
College of Chest Physicians 2008
guidelines.65 Additionally, both groups
suggest that unfractionated heparin
or low-molecular weight heparin can
be utilized in pregnancy either as a
bridge to warfarin therapy or as a
stand-alone treatment.64,65 Following
delivery, warfarin can be utilized for
anticoagulation which is generally
continued for a 3- to 6-month period with repeat imaging.

Seizures

Seizures in pregnant or post-partum
stage can be classified into three
categories: first, and most common, are
women with established epilepsy prior
to pregnancy;66 second group comprises
of non-pregnancy related seizures, like
new onset seizure from an structural
brain lesions or hypoglycemia; and
lastly, the third group comprises of
pregnancy related new onset seizures
(caused by eclampsia, cerebral venous
thrombosis, reversible cerebral
vasoconstriction syndrome, posterior
reversible encephalopathy syndrome,
intracerebral hemorrhage or thrombotic
thrombocytopenic purpura).
Maternal seizures and antiepileptic
drugs can accentuate the risk of fetal
malformation approximately two
to three times. The conventional
anticonvulsant drugs (phenytoin,
valproate, and carbamazepine) carry
almost similar overall risk. Valproate
and Carbamazepine are associated with
a higher risk of spina bifida (about 1% for
carbamazepine and 2% for valproate).67,68
Polytherapy appears to increase the
risk of fetal malformations.69,70 Folate
supplementation is vital to reduce the
risk of spina bifida.
Generalised tonic-clonic seizures can
lead to profound fetal bradycardia.71,72
Status epilepticus may be associated
with poor prognosis and death of
the child or mother, have both been
reported as a consequence. Treatment
protocol for status epilepticus in
pregnancy remains the same as in
general cases.73 Mothers who are kept
on antiepileptic enzyme inducing drugs
should be given 20 mg oral vitamin
K1 daily for a week prior to delivery.
If the exact date of delivery is not
known in advance which is a usual
situation, it seems sensible to start K1
a month before the expected delivery
date.74 Alternatively, the mother can
be given 10 mg K1 parenterally during
labour. Administration of vitamin
K1 to the newborn is recommended
in these circumstances. Most of the
anticonvulsant drugs apparently
pass into breast milk, albeit in very
low concentrations, which is not
likely to have any adverse effect on
infant.75 Breast feeding can therefore
be encouraged.

Posterior Reversible
Encephalopathy Syndrome (PRES)
commonly presents with headache,
seizures, encephalopathy, and visual
disturbances.
Clinical Setting: Acute hypertension,
pre-eclampsia or eclampsia, renal
disease, sepsis, and other conditions and
in those exposed to immunosuppressant
and other drugs.82-84
Clinical Features: Nearly 90% of
seizures might be focal to start along
with secondary generalization, and
generally precede visual changes
or headache, which is generally
dull, bilateral, and not thunderclap.
Confusion is common and may progress
to more significant degrees of altered
awareness including stupor or coma.85
40% of cases have visual symptoms
such as visual hallucinations, blurred
vision, scotomata, and diplopia.86
Nearly, 1-15% of patients have transient
cortical blindness.
Etiopathogenesis: Impairment in
underlying cerebral autoregulation
and/or endothelial dysfunction.82
Course: Symptoms often develop
without a prodrome and progress
rapidly over 12-48 hours. Visual
symptoms often resolve completely
in hours to days while the resolution
of oedema on imaging lags behind.87,88
CT Finding: Vasogenic oedema
mostly involves occipital lobe
MRI Finding: Focal oedema, in the
parieto-occipital lobes. Unlike posterior
cerebral artery lesions, the occipital
lesions spare the medial occipital lobe
and calcarine cortex.
Treatment: Emergent delivery if
feasible and appropriate. Magnesium
sulfate is commonly used for seizure
control.23
Differential Diagnosis : The
distribution of the lesions usually
involves multiple vascular territories
that help to distinguish the changes
from ischemic stroke.

Conclusions

Pregnant and post - partum
patients who present with new acute
neurological symptoms need a thorough
diagnostic evaluation that targets
a range of pathological conditions
that are either unique to or arise
more frequently in this population.
Appropriate management, preferably
under the joint care of obstetricians,
neurologists, neurosurgeons, and
paediatricians in established centres,
will ensure successful foetal and
maternal outcomes.